Purpose:
Glaucoma is a neurodegenerative disease, which leads to irreversible blindness by a continuous loss of axon density of the optic nerve. An elevated intraocular pressure (IOP) and its fluctuations are considered as major risk factors. Furthermore, complex alterations of autoantibody profiles were identified in serum of glaucoma patients, indicating an involvement of an autoimmune component in this disease. The aim of the study was to identify the systemic influence of fluctuations by use of intermittent pressure peaks and drops in an innovative animal model.<br />

Methods:
Sedated male Long Evans rats experienced a unilateral, intermittent IOP manipulation using a silicone loop adjusted around the eye globe for 1 hour during 27 treatments. The pressure profile included pressure peaks to 35 and 45 mmHg and drops to a physiologic value of 8 mmHg, thus recreating a comparable pressure profile of a glaucoma patient. Contralateral (n=12) and untreated eyes (n=14) served as controls. The degree of axonal damage was determined after paraphenylenediamine staining of optic nerve cross-sections. Retinal thickness was analyzed using Spectralis OCT with a rodent-specific setup. Changes of serum immunoreactivities were identified using a microarray approach with a glaucoma-specific antigen setup.

Results:
A cumulative IOP exposure of +748±12 mmHg implied a loss of axon density (as axons/0.05 mm2) of treated eyes (19624±1709) compared to contralateral (21943±1510; p<0.01) and untreated eyes (22267±1408; p<0.01). A slight increase of the retinal thickness in treated eyes was detected (191.9±4.2 µm) in comparison to contralateral (190.2±6.7 µm) and control eyes (188.4±5.1 µm). Upregulated immunoreactivities for glutathione S-transferase, transferrin, gamma-synuclein and neuron-specific enolase were identified in serum of treated animals in comparison to control serum (p<0.05).

Conclusions:
This glaucoma animal model including pressure peaks and drops allows the establishment of IOP profiles approximate to those observed in glaucoma patients. A vertical expansion of the retina, which might be based on retinal swelling or edema, was observed in treated animals. Indeed, a glaucomatous-like pathophysiology evidenced by an impaired optic nerve and an altered autoimmune repertoire could be induced. A tremendous influence of pressure fluctuations could be demonstrated using this sophisticated glaucoma animal model.